O' Grady started boxing professionally in 1975. In 1980, he had his first world title try, when the WBC gave him a shot at their world Lightweight championship. O' Grady travelled to Scotland and faced world champion Jim Watt, only to sustain a cut early in the bout and lose by a tehnical knockout in round 12. The O' Gradys protested the fight's result, arguing that the cut had been caused by a headbutt, not a punch. Because of the controversy surrounding the fight, the world's other leading boxing body of the time, the WBA, took O' Grady into consideration and gave Sean a second try at becoming world champion, this time against the WBA's world champion, Emanuel Steward trained Hilmer Kenty, on April 12 of 1981. O' Grady again suffered a cut early in the bout, but he dropped Kenty in round eight and won a unanimous decision, to become a world champion. The fight was one of the ten best fights of 1981, according to Ring Magazine.
O' Grady and his father then got distanced, a fact that worked against Sean. In part because of his problems with his father, he could never defend his world title, and he was stripped of it by the WBA about six months after winning it. But father and son eventually made up, and Pat O' Grady then formed the little regarded (and very short lived) WAA, to recognize Sean as a champion. This title did not meant much to most of the rest of the boxing world, and O' Grady promptly lost it, to Andy Ganigan of Hawaii.
After that fight, he retired from boxing, and has been able to stay retired ever since. However, O' Grady did not leave the public eye after his career as a boxer was over. If anything, he became more noticeable to the public. Soon, he signed a contract with the USA Network to be a television broadcaster. He covered all types of boxing fights there until 1994, when their show, USA Tuesday Night Fights, decided to have a curtain call. He then went on to broadcast fights with Fox Sports Network, and he lended his voice for the video game, Knockout Kings. In 1999, he started appearing as a color commentator on the Toughman tv show at the F/X channel. He also has an instructional video named How to Box by Sean O' Grady, and in 1992, he was inducted into the World Boxing Hall of Fame (not to be confused with the more generally accepted, International Boxing Hall of Fame).
O' Grady had a record of 81 wins and 5 losses as a professional boxer, with 70 wins by knockout, making him a member of the exclusive group of boxers with 50 or more career knockout wins.